Abstract
Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645–648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 325-334 |
| Number of pages | 10 |
| Journal | Biophysical Journal |
| Volume | 66 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 1994 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biophysics
Cite this
Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism. / Kienker, P.; Tomaselli, Gordon F.; Jurman, M.; Yellen, G.
In: Biophysical Journal, Vol. 66, No. 2, 01.01.1994, p. 325-334.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism
AU - Kienker, P.
AU - Tomaselli, Gordon F.
AU - Jurman, M.
AU - Yellen, G.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645–648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.
AB - Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645–648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028118783&partnerID=8YFLogxK
U2 - 10.1016/S0006-3495(94)80781-7
DO - 10.1016/S0006-3495(94)80781-7
M3 - Article
VL - 66
SP - 325
EP - 334
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 2
ER -